Modulation of mu, kappa and delta opioid receptors in the rat brain by isoflurane and enflurane

Abstract

This study was done to investigate whether inhalational anesthetics modulated the binding of specific ligands to opioid receptors in the brain of the rat. The effect of isoflurane and enflurane on the binding of specific ligands to various subtypes of opioid receptors in vitro was studied. Isoflurane inhibited the binding of [ 3H]naloxone to opioid receptors by 50% in the spinal cord, midbrain and cortex at 22, 49 and 50 mM, respectively. Enflurane was more potent than isofiurane in inhibiting the binding of [ 3H]naloxone. Scatchard analysis of the binding of [ 3H]naloxone, done in the presence of therapeutic level (5 mM) of isoflurane, suggested that it did not affect the K D(1.3 nM) but decreased the B max by 41% in the cortex. Isoflurane and enflurane, at large doses (30–50 mM), inhibited the binding of [ 3H]ethylketocyclazocine (EKC) to kappa receptors in midbrain, cortex and spinal cord. At a smaller dose (5 mM), they increased the binding of EKC in spinal cord. The binding of the analogs of enkephalin [ 3H]DSTLE(Tyr- D Ser-Gly-Phe-Leu-Thr-enkephalin) to delta receptors and [ 3H]DAGO (Tyr-D-Ala-Gly-Methyl-Phe-Glyol-enkephalin) to mu receptors in the midbrain and cortex was inhibited by isoflurane at a significantly smaller concentration than the binding of [ 3H]naloxone, indicating that the binding of peptides was more susceptible to the inhibition by inhalational anesthetics than the binding of alkaloids, such as naloxone or EKC. These results suggest that the modulation of opioid receptors by inhalational anesthetics is a function of both the nature of the ligand and the tissue used for the receptor binding. In addition, the inhibition of opioid receptors by inhalational anesthetics was greater in the spinal cord than in the cortex or midbrain. Only in the spinal cord did inhalational anesthetics, at therapeutic doses, increase the binding of kappa agonists. Isoflurane increased the K D and B max for EKC in the spinal cord.